Field of the Invention
The present invention provides methods of preparing active immunoconjugates, including anti-CD22 immunoconjugates. Suitably, the methods include a fed-batch process and/or column elution process that result in an increase in yield of the immunoconjugate over other processes that do not utilize the methods.
Background Art
The large-scale, economic purification of proteins is a critical factor in production in the biopharmaceutical industry. Therapeutic proteins are typically produced using prokaryotic or eukaryotic cell lines that are engineered to express the protein of interest from a recombinant plasmid containing the gene encoding the protein. Separation of the desired protein from the mixture of components fed to the cells and cellular by-products to an adequate purity, e.g., sufficient for use as a human therapeutic, poses a formidable challenge to biologics manufacturers for several reasons.
Manufacturers of protein-based pharmaceutical products must comply with strict regulatory standards, including extremely stringent purity requirements. To ensure safety, regulatory agencies, such as Food and Drug Administration (FDA), require that protein-based pharmaceutical products are substantially free from impurities, including both product related contaminants such as aggregates, fragments and variants of the recombinant protein and process related contaminants such as host cell proteins, media components, viruses, DNA and endotoxins. While various protein purification schemes are available and widely used in the biopharmaceutical industry, they typically include an affinity-purification step, such as Protein A purification in the case of antibodies, in order to reach a pharmaceutically acceptable degree of purity.
The development of a purification scheme applicable to both a particular biomolecule and various biomolecules that is scaleable, controllable, and provides for high yield of a purified biomolecule, will allow its integration into product development at a very early stage in overall drug development. Therefore, it is desirable and advantageous to provide a simple and efficient process that can produce a drug substance of high quality and safety.